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Synthesis of Cyanohydrins

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Very low loadings of a N,N-diethylacetamide derived phosphorane efficiently catalyze the cyanosilylation of a broad range of ketones. Aldehydes, aldimines, and ketimines are also viable substrates.
W.-B. Wu, X.-P. Zang, J. Zhou, J. Org. Chem., 2020, 85, 14342-14350.

Chiral oxazaborolidinium salts are excellent catalysts for a highly enantioselective cyanosilylation of various aldehydes using trimethylsilyl cyanide and triphenylphosphine oxide as the source of a new reactive cyanide donor. A mechanistic model allows the prediction of the absolute configuration of cyanohydrin products.
D. H. Ryu, E. J. Corey, J. Am. Chem. Soc., 2004, 126, 8106-8107.

A new chiral amino thiourea catalyst promotes the highly enantioselective cyanosilylation of a wide variety of ketones. The hindered tertiary amine substituent plays a crucial role with regard to both stereoinduction and reactivity, suggesting a cooperative mechanism involving electrophile activation by thiourea and nucleophile activation by the amine.
D. E. Fuerst, E. N. Jacobsen, J. Am. Chem. Soc., 2005, 127, 8964-8965.

A β-amino alcohol-Ti(Oi-Pr)₄ complex efficiently catalyzes a mild, enantioselective cyanosilylation of aldehydes. Aromatic, conjugated, heteroaromatic, and aliphatic aldehydes were converted to their corresponding cyanohydrin trimethylsilyl ethers in excellent yields with high enantioselectivities.
Y. Li, B. He, B. Qin, X. Feng, G. Zhang, J. Org. Chem., 2004, 69, 7910-7913.

Acylals derived from aliphatic aldehydes provide the corresponding cyanohydrin esters in good to excellent yields in the presence of KCN in DMSO at room temperature whereas acylals from aromatic aldehydes were less reactive and gave several byproducts. The combination of TMSCN and TiCl₄ afforded cyanohydrin esters in good to excellent yields from both aliphatic and aromatic aldehydes.
M. Sandberg, L. K. Sydnes, Org. Lett., 2000, 2, 687-689.

A highly efficient, direct C(sp³)-H cyanation under mild photocatalytic conditions offers excellent functional group tolerance. Notably, complex natural products and bioactive compounds were efficiently cyanated.
K. Kim, S. Lee, S. H. Hong, Org. Lett., 2021, 23, 5501-5505.

A simple, inexpensive, and highly enantioselective cyanohydrin synthesis with aromatic aldehydes using chiral lithium binaphtholate aqua or alcohol complexes has been developed that is suitable for process chemistry. Dramatic improvements in enantiomeric excess have been realized along with an interesting changeover in absolute stereochemistry of cyanohydrin product against the thoroughly "dry" catalytic systems.
M. Hatano, T. Ikeno, T. Miyamoto, K. Ishihara, J. Am. Chem. Soc., 2005, 127, 10776-10777.

Commercial montmorillonite K10 as catalyst enables a practical green protocol for highly efficient cyanosilylation of various ketones with excellent isolated yields. After use, the catalytic strength of the clay can be easily restored.
X. Huang, L. Chen, F. Ren, C. Yang, J. Li, K. Shi, X. Gou, W. Wang, Synlett, 2017, 28, 439-444.

Rasta resin-PPh₃BnCl, a heterogeneous polystyrene-based phosphonium salt, catalyzes cyanosilylation reactions of aldehydes and ketones efficiently. In these reactions, rasta resin-PPh₃BnCl was separated from the desired reaction product simply by filtration, and it could be reused without significant loss of catalytic activity numerous times.
Y. Teng, P. H. Toy, Synlett, 2011, 551-554.

Uncatalyzed cyanosilylation of ketones with NaCN and various chlorotrialkylsilanes in DMSO proceeds smoothly to give silyl-protected cyanohydrins in excellent yields. The role of DMSO consists in rendering naked cyanide anions that reversibly add to the carbonyl at the rate-determining step followed by fast sillylation of the transient tertiary alcoholates with chlorotrialkylsilanes or in situ generated cyanotrialkylsilanes.
F. L. Cabirol, A. E. C. Lim, U. Hanefeld, R. A. Sheldon, I. M. Lyapkalo, J. Org. Chem., 2008, 73, 2446-2449.

Gold(III) chloride is a highly efficient catalyst for the cyanosilylation of various ketones and aldehydes. The reactions were complete within 30 minutes at room temperature in the presence of only 1 mol% gold(III) chloride, yielding the corresponding cyanohydrin trimethylsilyl ethers in very good yields.
W. K. Cho, S. M. Kang, A. K. Medda, J. K. Lee, I. S. Choi, H.-S. Lee, Synthesis, 2008, 507-510.

1-Methoxy-2-methyl-1-(trimethylsiloxy)propene, a neutral π-nucleophile, is able to efficiently catalyze cyanosilylations and cyanocarbonations of various aldehydes and ketones.
X. Wang, S.-K. Tian, Synlett, 2007, 1416-1420.

An efficient, simple and mild method enables a cyano transfer from trimethylsilylcyanide (TMSCN) to aldehydes within 10 minutes at room temperature in the presence of 0.5 mol% of dispersed NbF₅ as the catalyst under solvent-free conditions giving cyanohydrins in excellent yields.
S. S. Kim, G. Rajagopal, Synthesis, 2007, 215-218.

Tertiary cyanohydrin trimethylsilyl ethers were synthesized in excellent yields by using a catalytic-amount of a salen-Al complex and an N-oxide without solvent at ambient temperature. Transition states for double-activation catalysis were proposed.
F.-X. Chen, X. Liu, B. Qin, H. Zhou, X. Feng, G. Zhang, Synthesis, 2004, 2266-2272.

N-Heterocyclic carbenes were found to be highly effective organocatalysts in activating TMSCN for facile and mild cyanosilylation of carbonyl compounds. Various trimethylsilylated cyanohydrins were isolated in very good to excellent yields.
J. J. Song, F. Gallou, J. T. Reeves, Z. Tan, N. K. Yee, C. H. Senanayake, J. Org. Chem., 2006, 71, 1273-1276.

An efficient method for achiral addition of TMSCN to ketones employs N-methylmorpholine N-oxide as catalyst. A variety of aromatic, aliphatic, cyclic and heterocyclic ketones are converted into their corresponding trimethylsilyl ethers in excellent yields (>90%).
Z.-G. Le, Z.-C. Chen, Y. Hu, Q.-G. Zheng, Synthesis, 2004, 208-212.

An N-heterocyclic carbene as a nucleophilic organocatalyst allows the cyanation of ketones and ketimines with TMSCN in good yields under mild reaction conditions.
Y. Fukuda, K. Kondo, T. Aoyama, Synthesis, 2006, 2649-2652.

Combinations of N-oxides and Ti(OiPr)₄ act as bifunctional catalysts in the cyanosilylation of ketones. The reaction is promoted by the dual action of these new titanium complexes via activation of the ketone by the titanium and of TMSCN by the N-oxide.
Y. Shen, X. Feng, Y. Li, G. Zhang, Y. Jiang, Tetrahedron, 2003, 59, 5667-6675.

A bimetallic titanium complex [(salen)TiO]₂ catalyzes the asymmetric addition of ethyl cyanoformate to aldehydes leading to cyanohydrin carbonates with high enantiomeric excesses.
Y. N. Belokon, A. J. Blacker, L. A. Clutterbuck, M. North, Org. Lett., 2003, 5, 4505-4507.

La(OiPr)₃ catalyzes a reaction of oxime esters or acid anhydrides with cyanotrimethylsilane (Me₃SiCN) to provide α-trimethylsilyloxydinitrile derivatives in excellent yields. The reaction seems to proceed through the formation of acyl cyanides as intermediates.
A. Fujii, S. Sakaguchi, Y. Ishii, J. Org. Chem., 2000, 65, 6209-6212.